Extracorporeal life support (ECLS) is a widely used technique in intensive care units to assist patients with severe organ deficiencies. Among the different ECLS techniques, extracorporeal membrane oxygenation (ECMO) provides life-saving temporary heart and lung support to patients who experience cardiac and/or respiratory failure unresponsive to standard ventilator and pharmacologic management. The clinical implementation of ECMO varies, but generally consists of a drain cannula through which blood is drained from the patient's venous system, a roller or centrifugal pump, a membrane oxygenator that oxygenates the blood and removes carbon dioxide, a bladder pressure module, a heat exchanger, and an arterial cannula through which the oxygenated blood is returned to the patient's arterial system.
Although the implementation of ECMO in the neonatal, pediatric and adult intensive care unit has been shown to result in improved survival rates, it is also associated with some complications. Patients treated with ECMO may experience acute renal failure due to combined renal hypoperfusion and hypoxemia as a result of their primary disease, resulting ultimately to a decreased urine output. Since illnesses leading to cardio respiratory failure can require large volumes of fluid resuscitation, patients often received large amounts of crystalloid and blood products during their pre-ECMO course and may develop serious fluid overload. This fluid overload is associated with pulmonary edema, worsening lung injury, and increased incidence of multiple organ failure in critically ill patients. Recent studies have suggested that improved fluid balance could be associated with improved outcomes in critically ill patients. Fluid restriction can be employed in management; however this is often at the expense of decreasing caloric intake, which could be detrimental to improving overall outcomes. Treating or preventing fluid overload in this setting can require aggressive use of diuretics, which has been suggested to worsen outcomes in critically ill adults with renal failure.
Renal support can be provided by a continuous renal replacement therapy (CRRT) such as continuous venovenous hemofiltration (CVVH). This technique allows for precise control of fluid balance by providing continuous fluid, electrolyte and toxin clearance even in the absence of adequate native renal function via convective processes through a permeable membrane. The hemofiltration retains proteins and cellular components of the intravascular space and eliminates plasma water and dissolved solutes. A typical CVVH setup consists of a hemofilter and a pair of pumps to achieve the drainage of the ultrafiltrate which is discarded and the delivery of replacement fluid, respectively. The portion of the ultrafiltrate that corresponds to body weight loss within a patient is discarded merely as removal filtrate. However, when the excess of the ultrafiltrate other than the removal filtrate is discarded, blood that has been filtered must be given a replacement fluid in an amount equal to the amount of the excess to maintain the water balance of the patient. It is known that most optimally the living body should be given replacement fluid continuously at the same rate as the discharge of the excess of ultrafiltrate. To meet these requirements, it is critical for CVVH systems to measure the amounts of the ultrafiltrate, excess ultrafiltrate and replacement fluid.
To supply the replacement fluid continuously in balance with the excess ultrafiltrate, systems have been proposed which include those of the type in which the volume of ultrafiltrate removed is determined by indirect measurements such as rate of removal of ultrafiltrate or weight of the ultrafiltrate removed. Such systems inherently are inaccurate because they are using surrogates to determine volume. In such systems, there shall always be an error within the volume determination because the measurements are not directly on volume itself. The error that occurs may be small and insignificant when treating patients of an adult size. However, when these errors are scaled down and the patient is a 3 kilogram infant, the errors become significant, causing the patient to be thermodynamically unstable
CVVH has also been used in combination with other extracorporeal therapies, including ECMO. In that configuration, a single roller pump drives simultaneously the blood in the ECMO and CVVH circuits. Blood from the oxygenator is drained to the hemofilter and returns to the ECMO circuit via the ECMO bladder. A recent study reported that percent fluid overload was correlated with mortality in patients receiving CVVH. In another case report, the benefits of a combined ECMO-CVVH therapy were assessed to treat neonatal cardiac and respiratory failure. The results demonstrated that the reduction of fluid overload via CVVH could lead to a significant improvement in both oxygenation and cardiac output. Finally, similar benefits were observed when implementing CVVH along with ECMO in the pediatric intensive care unit. Those results suggest that the use of CVVH during ECMO is associated with improved fluid balance and caloric intake with less use of diuretics compared to standard ECMO approaches.
Significant issues associated with the implementation of this combined therapy are the complexity, cost, staffing requirements, and increased risk to an already complicated and expensive ECMO course of action. Although devices such as the Diapact (B. Braun Medical Inc., Bethlehem, Pa.) and the Prisma (Gambro Dasco S.p. A., Medolla, Italy) are commercially available and use a weight-based method of ensuring accuracy, no commercially available CRRT device is specifically approved for use in conjunction with ECMO. Additionally, the Diapact's use is limited in neonatal and pediatric patients because the lowest ultrafiltration rate is 300 ml/hour and many patients in pediatric care require less than that. There is a need for a simplified ECMO-CVVH setup which may solve these and the many other potential problems associated with current ECMO-CVVH systems.
When using ECMO-CCVH systems, close attention is required to assess patient level of hydration as some inaccuracy in pump delivery of replacement fluid volume and pump extraction of ultrafiltrate fluid volume can occur, creating the potential for excessive fluid removal. Clinical experience has suggested that significant differences between set and observed fluid removal rates can occur, leading to cases of dehydration out of proportion to desired rates. Preliminary observations suggested that this difference might be due to replacement fluid pump inaccuracy of up to 12.5%. This inaccuracy has discouraged some ECMO physicians from using this potentially beneficial technique due to the lack of a simple and accurate intravenous fluid pump system capable of working against high flow rates seen in patients on ECMO. There is a need for an ECMO-CVVH system that also solves these problems.
Many patients not receiving ECMO also require renal replacement therapy in the intensive care unit while they are ill. CVVH is a common method of providing renal replacement therapy to critically ill and hemodynamically unstable patients in the pediatric intensive care unit. There is currently no FDA approved CVVH device for use in the neonatal and pediatric populations. Currently, because there is no other available choice approved for pediatrics and the fact that untreated renal failure can lead to death, physicians may resort to utilizing CVVH devices approved for adults to treat children. However, when adult approved CVVH devices are used on smaller patients, similar inaccuracy in fluid management as described above occur and complications are common.
There exists a need for systems and methods for fluid management for accurate continuous venovenous hemofiltration, which in some instances is combined and integrated with extracorporeal membrane oxygenation. In prior art systems in which a fluid management system is integrated with an ECMO system, as illustrated in FIG. 1, blood is filtered via a hemofilter 120 and the ultrafiltrate 125 is extracted from the hemofilter 120 via a first pump 130. Simultaneously, a second pump 135 delivers some replacement fluid 140 back into the filtered blood within the bladder 105. The main disadvantage of the combined system illustrated in FIG. 1 is the large pressure under which the ECMO circuit operates. The use of IV pumps 130, 135 to deliver or extract high flow rates of fluids under a pressure much higher than in the human body is controversial. The accuracy of a typical IV pump was tested in terms of the error between the programmed flow rate and the actual flow rate delivered by the pump for a range of pressures between 120 and 180 mmHg. The experiments that were repeated at three different flow rates (i.e., 1 L/hour, 500 mL/hour and 300 mL/hour) revealed an error increasing as a function of pressure and as a function of flow rate, illustrated in FIG. 2. Therefore, operating the two IV pumps of the CVVH circuit under the typical pressure of the ECMO circuit could lead to an increased ultrafiltrate removal from the patient and decreased fluid replacement to the patient. This phenomenon that has been observed to be more significant in smaller patients could result in rapid dehydration and could ultimately lead to shock. There is a need for a combined CVVH and ECMO system that solves this problem.
There also exists a need for a stand alone CVVH system designed specifically to provide accurate fluid management therapy across the range of size and weight seen from infancy to adulthood. There exists a need for systems and methods for fluid management capable of producing either perfect or negative fluid balance between ultrafiltrate removal and replacement fluid delivery. There also exists a need for systems and methods for fluid management capable of achieving electrolyte replacement over a range of flow rates needed to care for patients ranging from neonates to adults. Finally, there exists a need for systems and methods for fluid management that preserves patient safety, maintains sterility, is easy to operate, and is compact enough to fit near a patient's bed.